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1.
Drug Discov Today ; 28(10): 103732, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37541423

RESUMO

External innovation initiatives in the pharmaceutical industry have become an integral part of research and development. Collaborations have been built to enhance innovation, mitigate risk, and share cost, especially for neurodegenerative diseases, a therapeutic area that has suffered from high attrition rates. This article outlines the Eisai-University College London (UCL) Drug Discovery and Development Collaboration as a case study of how to implement a productive industry-academic partnership. In the first 10 years, seven projects have been established and the first project, a novel anti-tau antibody for Alzheimer's disease, has entered clinical trials, providing early validation of this collaboration model.


Assuntos
Doença de Alzheimer , Descoberta de Drogas , Humanos , Universidades , Londres , Doença de Alzheimer/tratamento farmacológico , Indústria Farmacêutica
3.
PLoS Genet ; 9(2): e1003280, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23468640

RESUMO

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases.


Assuntos
Doença de Huntington/genética , Proteínas/genética , Expansão das Repetições de Trinucleotídeos/genética , Repetições de Trinucleotídeos/genética , Animais , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Instabilidade Genômica , Humanos , Camundongos , Proteína 3 Homóloga a MutS , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Neostriado/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo Genético , Estabilidade Proteica
5.
Nat Rev Cancer ; 10(12): 812, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21155177
6.
Nat Rev Cancer ; 10(12): 814, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21155178
7.
Nat Rev Genet ; 11(12): 815, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21063439
8.
Nat Rev Cancer ; 10(10): 664, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21080563
9.
Nat Rev Cancer ; 10(10): 667, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21080569
10.
Nat Rev Cancer ; 10(11): 737, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21080579
11.
Nat Rev Cancer ; 10(11): 738, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21080584
12.
Nat Rev Cancer ; 10(11): 740, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21080588
13.
Nat Rev Genet ; 11(11): 748, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20953212
14.
Nat Rev Genet ; 11(11): 749, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20921960
15.
Nat Rev Genet ; 11(10): 670-1, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20838409
16.
Nat Rev Cancer ; 10(9): 597, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20803807
17.
Nat Rev Cancer ; 10(9): 603, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20803814
18.
Nat Rev Genet ; 11(10): 672, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20733592
19.
Nat Rev Cancer ; 10(8): 530-1, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20677350
20.
Nat Rev Cancer ; 10(8): 535, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20677356
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